"Although their transient production triggers protective responses, their accumulation sustains inflammation, contributing to tissue damage," Di Gioia and Zanoni wrote.

The review ties oxPL accumulation to a broad set of conditions, drawing largely on emerging studies:

• Various cancers
• Metabolic disorders
• Infections
• Asthma
• Inflammatory bowel disease
• Neurodegenerative disorders
• Pain syndromes
• Aging

Historically, scientists viewed oxPLs as benign byproducts of oxidative stress. The Harvard team now treats them as potent bioactive molecules that bind specific receptors on immune cells, trigger intracellular signaling pathways and disrupt cellular homeostasis.

The reviewers note that polyunsaturated fatty acids, cholesterol and cholesterol intermediates can undergo enzymatic oxidation and serve as signaling molecules that alter tissue homeostasis and immunity.

Why are they called 'double-edged swords'?

The same compound class can produce opposite biological effects. Structural differences between individual oxPLs, combined with the receptors they bind on different cell types, drive divergent outcomes. The authors emphasize that one molecule can act as a benign agent or a source of substantial harm.

"These distinct classes of oxidized lipids not only share overlapping inflammatory roles but also exhibit divergent effects depending on their molecular structures and cellular targets," they wrote.

What happens inside tumors?

Inside the harsh tumor microenvironment, oxPLs accumulate abundantly. The molecules suppress neighboring T cells, the immune system's primary cancer fighters, and allow malignancies to evade immune attack.

The review also notes that oxPLs shape cell death programs and stromal cell behavior, two processes that favor tumor growth. Stromal cells are the supportive connective-tissue cells that surround tumors.

What advances do the authors call for?

The full scope of oxPL activity in human tissue remains unknown. Current analytical tools limit how thoroughly scientists can map lipids in different organs and disease states.

Di Gioia and Zanoni call for two key technological advances:

• High-resolution lipidomics, to identify individual lipid species in tissue samples
• Chiral chromatography, to separate molecules with identical formulas but different three-dimensional shapes

These tools could define which specific oxPLs drive disease in each tissue type. They could also help researchers design targeted therapies that block harmful lipid activity without disrupting protective functions.

"Addressing these limitations will be critical for ... the development of therapeutic strategies that selectively target pathogenic lipid oxidation or its downstream biological responses," the authors concluded.

If researchers learn to decode and control oxPL behavior, the review suggests, new therapies for cancer, chronic inflammatory disease and age-related decline could eventually follow.